The purpose of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil CD64 expression for bacterial infection in febrile adult patients presenting to our hospital emergency department. We prospectively included 132 patients with fever ≥ 38ºC (≥ 100.4ºF) during the last 24 hours and we measured CD64 expression on neutrophils the day after admission at the emergency department. We followed the patients until full recovery or death. There were 115 (87%) patients with bacterial infection and 108 (94%) of them survived. There were 17 (13%) patients without bacterial infection and 12 (71%) of them survived. Patients with bacterial infection and patients who survived showed a CD64 index higher when compared with patients without bacterial infection and patients who died, respectively (3.7 ± 3.2 vs. 2.5 ± 2.3; p = 0.03; and 3.7 ± 3.1 vs. 1.7 ± 0.6; p = 0.002; Mann-Whitney U test). The receiver operating characteristic (ROC) curve analysis for detecting bacterial infection and predicting survival with the CD64 index showed an area under curve (AUC) of 0.66 (95% CI, 0.52-0.8; p = 0.03) and 0.71 (95% CI, 0.57-0.85; p = 0.01), respectively. Diagnostic accuracy and prognostic value of CD64 expression was good in adult patients with fever.